Circadian (biological) clocks impose daily periodicities to many behaviors and physiological processes in a wide variety of organisms. In humans, the activity of circadian clocks impinges directly on many biological, medical, and societal aspects of life. These include sleep/wake cycles, alertness, jet lag, sensitivity to drugs and hormones, etc. In all systems examined so far, the expression of a rhythmic phenotype is due to the activity of cells with circadian pacemaker activity. Currently much is known about the molecular mechanism that produces circadian rhythmicity within these pacemaker cells. By contrast, comparatively less is known about how the activity of circadian pacemakers causes the behavioral and physiological outputs to be rhythmic. The aim of this exploratory proposal is to investigate the mechanism whereby the circadian clock imposes circadian rhythmicity to a behavioral output using Drosophila melanogaster as model system. In Drosophila, the circadian clock restricts the time of emergence of the adult to the early part of the (subjective) day. The circadian regulation of the time of emergence depends on the actions of, and interactions between, a central and a peripheral pacemaker. The emergence of the adult is the culmination of the process of metamorphosis, which is under direct control of the molting hormone that is produced by the peripheral pacemaker. However, this pacemaker is likely to be controlled by the central pacemaker, which may also regulate the timing of emergence directly. We will use direct measurements as well as genetic approaches to determine the contribution of each pacemaker to the timing of adult emergence. For this we will investigate the relationship between the timing of the completion of metamorphosis, the time course of molting hormone titers, the activity of the central and peripheral circadian pacemakers, and the timing of emergence behavior. The circadian timing of adult emergence is an ideal system for discovering the principles by which clocks produce rhythms of behavior and physiology because much is known about the Drosophila clock as well as about the endocrine mechanism that controls adult emergence behavior. Thus it offers a unique opportunity to elucidate how the activity of the clock is coupled to the mechanism that controls a behavioral output. [unreadable] [unreadable] [unreadable]